Sequential activation of RhoA and FAK/paxillin leads to ATP release and actin reorganization in human endothelium

• DOI: 10.1113/jphysiol.2004.065334
• Publication Date: 2004-05-25T00:53:34Z
• Authors: Masakazu Hirakawa; Masahiro Oike; Yuji Karashima; Yushi Ito
• Keywords: Paxillin; Stress fiber; MDia1; PTK2

We have investigated the cellular mechanisms of mechanical stress-induced immediate responses in human umbilical vein endothelial cells (HUVECs). Hypotonic stress (HTS) induced ATP release, which evoked a Ca(2+) transient, followed by actin reorganization within few minutes, HUVECs. Disruption cytoskeleton did not suppress HTS-induced and inhibition ATP-mediated response affect reorganization, thereby indicating that these two are interrelated. release were also lysophosphatidic acid (LPA). HTS LPA membrane translocation RhoA, occurs when RhoA is activated, tyrosine phosphorylation focal adhesion kinase (FAK) paxillin. Tyrosine inhibitors (herbimycin A or tyrphostin 46) inhibited both HTS- LPA-induced but activation. In contrast, Rho-kinase inhibitor (Y27632) all responses. These results indicate activation RhoA/Rho-kinase pathway FAK paxillin leads to Furthermore, fact evoke exactly same intracellular signals suggests even mechanosensitive stress-specific.